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Related Concept Videos

Pharmacokinetics in Pediatric Patients: Overview and Drug Absorption01:23

Pharmacokinetics in Pediatric Patients: Overview and Drug Absorption

Understanding the physiological differences in the pediatric population is crucial for effective pharmacotherapy. Neonates, infants, and children exhibit significant variations in gastric pH, gastric emptying time, intestinal transit time, and biliary function. These variations profoundly affect oral drug absorption, necessitating a nuanced approach to pediatric dosing.Neonates present with a unique physiological profile, having a gastric pH greater than 4 and faster and more irregular gastric...
Pharmacokinetics in Pediatric Patients: Drug Distribution01:17

Pharmacokinetics in Pediatric Patients: Drug Distribution

Drug distribution in the pediatric population exhibits unique challenges and considerations due to the physiological differences between children, particularly neonates and infants, and adults. A crucial aspect of pediatric pharmacology is understanding how these differences impact the pharmacokinetics of various drugs, necessitating age-specific dosing strategies to ensure efficacy and safety.Neonates and infants have a higher total body water content, ~75%–90% of their body weight, compared...
Pharmacokinetics in Pediatric Patients: Drug Metabolism01:24

Pharmacokinetics in Pediatric Patients: Drug Metabolism

In pediatric care, understanding the nuances of hepatic drug metabolism is crucial, as it significantly differs from that of adults. This divergence is primarily due to the developmental stage of drug-metabolizing enzymes, which affects how medications are processed in the body. In neonates, for instance, the activity of Phase I enzymes—critical for the initial breakdown of drugs—is markedly reduced, functioning at just 20–40% of the levels seen in adults. This reduction poses a challenge in...
Pharmacokinetics in Pediatric Patients: Drug Excretion01:26

Pharmacokinetics in Pediatric Patients: Drug Excretion

In pediatric medicine, understanding the renal function and drug elimination nuances is crucial for administering safe and effective treatments. Newborns, in particular, display markedly slower renal functions than adults, profoundly affecting how drugs are cleared from their bodies. This slower drug clearance requires clinicians to extend the dosing intervals for many medications to prevent drug accumulation and toxicity while ensuring therapeutic efficacy.One key area where these adjustments...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
Antiprotozoal Agents01:21

Antiprotozoal Agents

Leishmaniasis is a widespread parasitic disease caused by several Leishmania species. It affects millions of people each year and remains a major public health problem in endemic regions. First-line treatment relies on pentavalent antimonials, including meglumine antimoniate and sodium stibogluconate. Even so, how these drugs work has not been fully clear, especially their interaction with parasite-specific biochemical pathways. One key target is trypanothione reductase (TR), an enzyme that...

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Pharmacology of all-trans-retinoic acid in children with acute promyelocytic leukemia.

Claudia Lanvers1, Dirk Reinhardt, Angelika Dübbers

  • 1University Children's Hospital Muenster, Department of Pediatric Hematology and Oncology, Albert-Schweitzer-Str. 33, Germany.

Medical and Pediatric Oncology
|March 26, 2003
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Reduced doses of all-trans-retinoic acid (ATRA) for acute promyelocytic leukemia (APL) in children still cause toxicity. Intermittent dosing may be a safer alternative to further dose reduction in pediatric APL treatment.

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Area of Science:

  • Pediatric Oncology
  • Pharmacology
  • Hematology

Background:

  • Standard all-trans-retinoic acid (ATRA) dosage for acute promyelocytic leukemia (APL) in children causes severe side effects.
  • The AML-BFM study group reduced the ATRA dosage to 25 mg/m(2)/day for pediatric APL treatment.
  • Limited data necessitated an evaluation of ATRA pharmacokinetics and metabolism in children at the reduced dose.

Purpose of the Study:

  • To assess the pharmacokinetics and metabolism of all-trans-retinoic acid (ATRA) in pediatric patients with acute promyelocytic leukemia (APL).
  • To investigate the variability in ATRA plasma concentrations and identify potential factors contributing to toxicity in children.
  • To explore alternative dosing strategies for ATRA in pediatric APL treatment to mitigate side effects.

Main Methods:

  • Analyzed pharmacokinetic and metabolic profiles of ATRA in 14 children with APL (0.9-18.4 years).
  • Collected and analyzed 11 plasma samples over 8 hours using high-performance liquid chromatography.
  • Measured ATRA and its metabolites, alongside plasma vitamin A concentrations.

Main Results:

  • Observed wide interpatient variability in peak plasma ATRA concentrations (28.6-513.0 nM).
  • Identified similar metabolic pathways in children compared to adults.
  • Despite lower effective in vitro concentrations, neurotoxicity occurred in 8 patients, requiring dose adjustments; higher vitamin A levels correlated with neurotoxicity (P=0.03).

Conclusions:

  • Low plasma ATRA concentrations and persistent toxicity suggest current dosing may be suboptimal.
  • Intermittent ATRA dosing could be a viable alternative to further dose reduction in pediatric APL.
  • Consideration of intermittent dosing is crucial for children at risk of ATRA-induced neurotoxicity.